AB0346 INTESTINAL MICROECOLOGICAL DISORDERS IN RHEUMATOID ARTHRITIS
Authors: X. Y. Yin, Q. Y. Su, J. N. Liu, J. Luo, Q. Yu, P. F. He, X. Li, S. X. Zhang
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by a persistent immune response leading to arthritis and destruction. Mounting evidence has suggested that dysbiosis of the intestinal microbiome is a vital environmental element that triggers the onset of RA[1]. Unraveling the interactions between the gut microbiome and metabolome could provide new insights to discover novel targets for treating various inflammatory diseases. However, the current understanding of the potential association between intestinal microbiota and RA still needs to be improved. <h3>Objectives</h3> Recent studies have reported that the change in the interaction between the microbiome and the immune system is one of the characteristics of RA. Therefore, we conducted a meta-analysis and Mendelian randomization(MR) to explore the association and causality between RA and intestinal flora. <h3>Methods</h3> The PubMed, Embase, Medline, Web of Science, CNKI, Wanfang, VIP, and CBM databases were searched from the establishment of the databases to January 1, 2023, to retrieve trials about RA and intestinal flora. We performed a meta-analysis to calculate the odds ratio(OR) and 95% confidence intervals (95%CI). In addition, we conducted a bi-directional MR study to explore the causal relationship between RA and intestinal microbial composition. Single nucleotide polymorphisms (SNPs) associated with RA from 22 genome-wide association studies (14,361 cases and 43,923 controls) were selected as instrumental variables (IVs) at a genome-wide significance level. The aggregated statistical data of intestinal microbiota were obtained from a large-scale multiracial GWAS meta-analysis, including 18,340 people from 24 cohorts. The random-effects inverse variance weighted method (IVW) was used to combine the causal effect of IVs. Sensitivity analyses were performed to test the robustness of our findings. All analyses were conducted in R 4.2.1 and STATA 12.0. <h3>Results</h3> We included 17 case-control studies that examined 1,062 RA patients and 921 healthy controls(HCs). Compared with HCs, decreases in α-diversity indices were consistently found in RA[Shannon-Wiener diversity index (SMD=-0.608, 95% CI -0.935 to -0.281, p&lt;0.001); Simpson index(SMD=-0.558, 95% CI -0.891 to -0.225, p&lt;0.001); ACE index(SMD=-0.414, 95% CI -0.697 to -0.132, p&lt;0.001); Chao1 index(SMD=-1.373, 95% CI -1.980 to -0.766, p&lt;0.001); Eveness index(SMD=-1.863, 95% CI -3.181 to -0.544, p=0.004)]. There was no significant difference in Observed_species between the two groups(SMD=-4.342, 95% CI -9.098 to 0.415, p&lt;0.001). Further, we conducted a bi-directional MR analysis to test the causal relationship between RA and intestinal microorganisms, which included three phyla(<i>Firmicutes, Proteobacteria, Actinobacteria</i>), six families(<i>Bacteroidaceae, Actinomycetaceae, Clostridiales, Lactobacillaceae, Bifidobacteriaceae, Lachnospiraceae</i>) and seven genera(<i>Bifidobacterium, Butyricicoccus, Escherichia Shigella, Lachnospiraceae, Lactobacillus, Actinomyces, Bacteroides</i>). However, no genetic prediction causal relationship was found between them (all p&gt;0.05). These results were robust in a wide range of sensitivity analyses. <h3>Conclusion</h3> This study suggested a significant correlation between RA and lower intestinal microflora abundance. This may provide new insight into the development mechanism of RA mediated by intestinal microbiota and may provide a evidence for regulating intestinal microecology to target the treatment of RA. <h3>Reference</h3> [1] Yu, D. et al. The Gut Microbiome and Metabolites Are Altered and Interrelated in Patients With Rheumatoid Arthritis. Front Cell Infect Microbiol 11, 763507, doi:10.3389/fcimb.2021.763507 (2021). <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.